Scientists begin to map neurodevelopment of schizophrenia.

Schizophrenia is generally considered to be a disorder of brain development and it shares many risk factors, both genetic and environmental, with other neurodevelopmental disorders such as autism and intellectual disability. The normal path for brain development is determined by the combined effects of a complex network of genes and a wide range of environmental factors.

However, longitudinal brain imaging studies in both healthy and patient populations are required in order to map the disturbances in brain structures as they emerge, i.e., the disturbed trajectories of brain development.

A new study by an international group of researchers, led by UT Southwestern, have measured neurodevelopment in schizophrenia, by studying brain development during childhood and adolescence in people with and without this disorder. With access to new statistical approaches and long-term follow-up with participants, in some cases over more than a decade, the researchers were able to describe brain development patterns associated with schizophrenia. The study is published in the journal Biological Psychiatry.

Specifically, the team have shown that parts of the brain’s cortex develop differently in people with schizophrenia. The mapping of the path that the brain follows in deviating from normal development provides important clues to the underlying causes of the disorder.

The findings were derived by investigating the trajectory of cortical thickness growth curves in 106 patients with childhood-onset schizophrenia and a comparison group of 102 healthy volunteers. Each participant, ranging from 7 years of age, had repeated imaging scans over the course of several years. Then, using over 80,000 vertices across the cortex, the researchers modelled the effect of schizophrenia on the growth curve of cortical thickness.

This revealed differences that occur within a specific group of highly-connected brain regions that mature in synchrony during typical development, but follow altered trajectories of growth in schizophrenia.

The findings show a relationship between the hypothesis that schizophrenia is a neurodevelopmental disorder and the longstanding hypothesis, first articulated by the German anatomist Karl Wernicke in the late 19th century, that it is a disease of altered connectivity between regions of the brain.

This theoretical consistency is important, as it allows researchers to better focus future studies of brain connectivity in schizophrenia, by targeting the brain regions known to be affected.

Abnormalities of growth curves in childhood-onset schizophrenia (COS) for each of the ~80,000 cortical vertices, using penalized spline models and false discovery rate (FDR)-adjusted p values. (A) Cortical regions with any difference in the maturational trajectory in COS, either a constant trait difference or an age-varying trajectory difference. In other words, the null hypothesis H0, that βv (age) in equation (2) is identically zero, is rejected. (B) Regions for which the null hypothesis H0a that Math Eq in equation (3) is rejected. All of these regions are, in fact, thinner in COS. The plot below shows the average maturational trajectory of these regions with 95% confidence intervals. (C) Regions with significant group differences in trajectory, i.e., the null hypothesis H0b that Math Eq is identically zero in equation (3) is rejected. The plot below shows the average maturational trajectory of these regions with 95% confidence intervals. Abnormal Cortical Growth in Schizophrenia Targets Normative Modules of Synchronized Development. Alexander-Bloch et al 2014.